FAYETTEVILLE, Ark. — Discovering how an enzyme that is regulated by insulin affects fat metabolism may hold the key to understanding obesity-related diabetes and other diseases. University of Arkansas researcher Michael Lehmann has won a $150,000 grant from the National Institutes of Health to study a protein whose activity is controlled by the insulin-sensitive enzyme TOR, or target of rapamycin. TOR is at the center of an important pathway that controls cell metabolism and growth in organisms as diverse as yeast and humans.

Cells that lack TOR act as if they are starved even if food is readily available.

“These cells 'think’ they are starved even if nutrients are abundant and so they stop growing,” said Lehmann, an associate professor in the J. William Fulbright College of Arts and Sciences. “If, under normal conditions, sufficient nutrients are available, TOR becomes active and promotes cell growth and fat storage. To understand how TOR controls these processes, it is important to identify the proteins that are modified by the enzyme and to study their functions.”

Lehmann is interested in one particular target of TOR, the protein lipin. Mice deficient in the lipin protein have underdeveloped fat tissue, and if the levels of lipin are artificially elevated, the mice become obese.

“This suggests that lipin mediates the effect of TOR specifically on fat metabolism, one of the hypotheses that we will test in the genetically more accessible fruit fly Drosophila,” said Lehmann. “We have evidence that lipin may also play a role in autophagy, which literally means 'self-digestion.’ TOR blocks such self-digestion, which is used by starved cells as a survival mechanism. We hope that through our studies we can discover how TOR inhibits this process.”

Obesity is viewed by many as the major current threat to public health in the U.S. Therapies targeting lipin could help alleviate obesity and associated conditions such as insulin resistance and diabetes. This study marks a new direction in research for Lehmann.